Composition for regulating blood sugar

ABSTRACT

The present invention provides a composition for regulating blood sugar. The composition comprises at least one yellow pigment extracted from a red mold product, wherein the said yellow pigment is Monascin, Ankaflavin, or combination of Monascin and Ankaflavin. Moreover, results of a variety of animal experiments have proved that this blood sugar regulating composition indeed possess the functionalities of: lowering Hyperglycemia induced by high energy diet, alleviating ROS and inflammatory caused by the Hyperglycemia, reduce AST and ALT value of liver as well as sarcosine value of kidney.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to the technology field of medically-usedcomposition, and more particularly to a composition for regulating bloodsugar.

2. Description of the Prior Art

American Diabetes Association (FDA) has published the way to judgewhether a person suffers from a diabetes mellitus (DM) or not. When theconcentration of fasting blood glucose (GLU-AC) of the person is higherthan 126 mg/dL or the concentration of 2 hours postprandial bloodglucose (2hPBG) of the person is higher than 200 mg/dL, the person isdiagnosed with diabetes mellitus. On the other hand, the person isdiagnosed with Impaired Glucose Tolerance (IGT) when the GLU-AC value ismeasured to fall in a range between 100 mg/dL and 126 mg/dL or the 2hPBGvalue falls in another one range between 140 mg/dL and 200 mg/dL. IGTmeans that blood glucose is raised beyond normal levels, but not highenough to warrant a diabetes diagnosis.

One of key factors to induce the occurrence of diabetes mellitus andmetabolism syndrome is Reactive Oxygen Species (ROS) resulted fromHyperglycemia, and ROS participate in the dysfunction of β-cell ofpancreas. In addition, insulin resistance often progresses to full Type2 diabetes mellitus (T2DM) or latent autoimmune diabetes of adults.Insulin resistance is often seen when Hyperglycemia develops after ameal and the pancreatic β-cells are unable to produce sufficient insulinto maintain normal blood sugar levels. Insulin resistance also decreasesthe translocation of glucose transporters (GLUT) to the cell membrane;and eventually, type 2 diabetes or latent autoimmune diabetes occurswhen glucose levels become higher throughout the day as the resistanceincreases and compensatory insulin secretion fails.

The statistical data made by Ministry of Health and Welfare of Taiwanshows that 90% T2DM patients does simultaneously suffer from obesity.The adipose tissue of an obesity patient may releases inflammationfactors such as hypoxia-inducible factor 1α (HIF-1α), tumor necrosisfactor-α (TNF-α) and interleukin (IL), wherein the excessive amount ofinflammation factors would induce lipolysis action to produce a largeamount of glycerin and free fatty acid (FFA), so as to aggravate theproduction of Hyperglycemia, fatty liver, and high blood ketone.Moreover, not only impelling the production of inflammation factors andROS, FFA also inhibits the activity of insulin receptor by activatingdiacylglycerol (DAG) and protein kinasenk C (PKC), so as to result inthe occurrence of insulin resistance.

Conventionally-used blood sugar reducing drugs include: non-sulfonylureainsulin secretagogue, sulfonylurea insulin secretagogue, biguanides,alpha-glucohydrolase inhibitor, and DPP-4 inhibitor (inhibitor ofdipeptidyl peptidase 4). However, all the above-mentioned blood sugarreducing drugs have side-effects with varying severity, such asdiarrhea, anorexia, nausea, and fatal lactic acidosis.

Insulin sensitizers are also the conventionally-used blood sugarreducing drugs, including troglitazone, rosiglitazone and pioglitazone.The insulin sensitizer possesses anti-diabetic activity throughactivation of a nuclear receptor called PPARγ (Peroxisomeproliferator-activated receptor γ). However, over-activation of PPARγdrives the unwanted and often unacceptable side effects associated withthe currently-approved insulin sensitizers, such as edema, weight gain,congestive heart failure, hepatotoxicity.

Thus, because the conventionally-used blood sugar reducing drugs maycause side-effects to DM patients, the inventor of the presentapplication has made great efforts to make inventive research thereonand eventually provided a composition for regulating blood sugar.

SUMMARY OF THE INVENTION

The primary objective of the present invention is to provide acomposition for regulating blood sugar. The composition comprises atleast one yellow pigment extracted from a red mold product, wherein thesaid yellow pigment is Monascin, Ankaflavin, or combination of Monascinand Ankaflavin. Moreover, results of a variety of animal experimentshave proved that this blood sugar regulating composition indeed possessthe functionalities of: lowering Hyperglycemia induced by high energydiet, alleviating ROS and inflammatory caused by the Hyperglycemia,reduce AST and ALT value of liver as well as sarcosine value of kidney.

In order to achieve the primary objective of the present invention, theinventor of the present invention provides a first embodiment of thecomposition for regulating blood sugar, comprising a yellow pigmentextracted from a red mold product, wherein the said yellow pigment isMonascin, and a first daily dosage of the Monascin for an adult user toregulate blood sugar is above 3 mg.

Moreover, for achieving the primary objective of the present invention,the inventor of the present invention provides a second embodiment ofthe composition for regulating blood sugar, comprising yellow pigmentextracted from a red mold product, wherein the said yellow pigment isAnkaflavin, and a second daily dosage of the Ankaflavin for an adultuser to regulate blood sugar is above 1.5 mg.

In addition, for achieving the primary objective of the presentinvention, the inventor of the present invention provides a thirdembodiment of the composition for regulating blood sugar, comprisingyellow pigment extracted from a red mold product, wherein the saidyellow pigment is a combination of Monascin and Ankaflavin, and a dailydosage of the combination for an adult user to regulate blood sugar isabove 4.5 mg; moreover, a first dose of Monascin in the combination isabove 3 mg and a second dose of the Ankaflavin in the combination isabove 1.5 mg.

Furthermore, for achieving the primary objective of the presentinvention, the inventor of the present invention provides a fourthembodiment of the composition for regulating blood sugar, comprising ared mold product produced by inoculating a Monascus purpureus to asubstrate and then subjecting the inoculated substrate with a culturingand drying process; wherein a fourth daily dosage of the red moldproduct for an adult user to regulate blood sugar is above 1 g.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention as well as a preferred mode of use and advantages thereofwill be best understood by referring to the following detaileddescription of an illustrative embodiment in conjunction with theaccompanying drawings, wherein:

FIG. 1 shows a curve plot of time versus blood glucose;

FIG. 2 shows a statistical bar graph of group versus AUC (area undercurve) of blood glucose;

FIG. 3 shows a statistical bar graph of adiponectin expression inadipose tissue;

FIG. 4 shows a statistical bar graph of ROS concentration in liver;

FIG. 5 shows a statistical bar graph of TNF-α expression in adiposetissue;

FIG. 6 shows a statistical bar graph of GLUT-2 expression in adiposetissue;

FIG. 7 shows a statistical bar graph of GLUT-4 expression in adiposetissue;

FIG. 8 shows a statistical bar graph of IL-1β expression in adiposetissue;

FIG. 9 shows a statistical bar graph of IL-1β expression in adiposetissue;

FIG. 10 shows a statistical bar graph of HIF-1α expression in adiposetissue;

FIG. 11 shows histomorphology images of liver slices.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

To more clearly describe a composition for regulating blood sugaraccording to the present invention, embodiments of the present inventionwill be described in detail with reference to the attached drawingshereinafter.

It is well known that Monascus species is divided into Monascus pilosus,Monascus purpureus, Monascus ruber, Monascus floridanus, Monascuspallens, and Monascus sanguineus. Moreover, according to culturepatterns, growth patterns, olors, and cleistothecia colors, the Monascusspecies is further divided into Monascus pilosus, Monascus purpureus,and Monascus ruber.

The present invention provides a composition for regulating blood sugar,wherein the composition comprises at least one yellow pigment extractedfrom a red mold product, wherein the said yellow pigment is Monascin,Ankaflavin, or combination of Monascin and Ankaflavin. It is worthwhileto explain that, the red mold product is produced by inoculating aMonascus purpureus to a substrate and then subjecting the inoculatedsubstrate with a culturing and drying process. The process steps forproducing the red mold product such as red mold rice (RMR) or red moldDioscorea (RMD) are full disclosed in the specification of TW patent NO.1415619. Moreover, in order to verify the practicability of the bloodsugar regulating composition proposed by the present invention, aparticularly-arranged of animal experiment is completed by inventers.After 1-week pre-feeding, several SD rats are divided into 9experimental groups for carrying out 10-week animal experiment.

First of the 9 experimental group is NOR group consisting of 8 SD rats,wherein the “NOR” means that the SD rats are fed with normal diet.During the animal experiment, the SD rats in NOR group are fed withcornstarch diet unlimitedly. Moreover, RO water is taken as test samplefor orally administering to SD rats in NOR group through feeding tubes.Second of the 9 experimental group is HFFD group consisting of 8 SDrats, wherein the “HFFD” means the SD rats are fed with high fat andfructose diet. During the animal experiment, the SD rats in HFFD groupare fed with chew diet consisting of 73.3% corn starch and 26.7% butterpowder.

Third of the 9 experimental group is MF group consisting of 8 SD rats,wherein the “MF” means that drug of Metformin is taken as test samplefor orally administering to SD rats in MF group through feeding tubes.Moreover, during the animal experimental, the SD rats in MF group arefed with high fat and fructose diet unlimitedly. Fourth of the 9experimental group is RMD group consisting of 8 SD rats, wherein the“RMD” means that powder of red mold Dioscorea (RMD) is taken as testsample for orally administering to SD rats in RMD group through feedingtubes. Moreover, during the animal experimental, the SD rats in RMDgroup are fed with high fat and fructose diet unlimitedly.

Fifth of the 9 experimental group is MS1X group consisting of 8 SD rats,wherein the “MS1X” means that 1-fold dosage of Monascin is taken as testsample for orally administering to SD rats in MS1X group through feedingtubes. Moreover, during the animal experimental, the SD rats in MS1Xgroup are fed with high fat and fructose diet unlimitedly. Sixth of the9 experimental group is MS5X group consisting of 8 SD rats, wherein the“MS5X” means that 5-fold dosage of Monascin is taken as test sample fororally administering to SD rats in MS5X group through feeding tubes.Moreover, during the animal experimental, the SD rats in MS5X group arefed with high fat and fructose diet unlimitedly.

Seventh of the 9 experimental group is AK1X group consisting of 8 SDrats, wherein the “AK1X” means that 1-fold dosage of Ankaflavin is takenas test sample for orally administering to SD rats in AK1X group throughfeeding tubes. Moreover, during the animal experimental, the SD rats inAK1X group are fed with high fat and fructose diet unlimitedly. Eighthof the 9 experimental group is AK5X group consisting of 8 SD rats,wherein the “AK5X” means that 5-fold dosage of Ankaflavin is taken astest sample for orally administering to SD rats in AK5X group throughfeeding tubes. Moreover, during the animal experimental, the SD rats inAK5X group are fed with high fat and fructose diet unlimitedly.

The last one of the 9 experimental group is MS-AK group consisting of 8SD rats, wherein the “MS-AK” means that a combination of 1-fold-doseAnkaflavin and 1-fold-dose Monascin is taken as test sample for orallyadministering to SD rats in MS-AK group through feeding tubes. Moreover,during the animal experimental, the SD rats in MS-AK group are fed withhigh fat and fructose diet unlimitedly. Herein, it needs to particularlyexplain that, the dosage for the above-mentioned different test samplesare integrated in following Table 1.

TABLE 1 Rat dosage Adult dosage Group Test sample (mg/kg*bw/day (mg/day)NOR RO water — — HFFD RO water — — MF Metformin 78.06 500 RMD Red mold104.17 1000 dioscorea MS1X Monascin 0.31 3 MS5X Monascin 1.56 15 AK1XAnkaflavin 0.16 1.5 AK5X Ankaflavin 0.78 7.5 MS-AK Monascin + 0.31 +0.16 3 + 1.5 Ankaflavin

The rat dosage for different test samples used in the 9 groups can becalculated by using following rat-adult dosage transforming equation:rat dosage=(adult dosage/60 kg)*6.25.

Determining Effects Provided by the Different Test Samples on the SDRats:

Please refer to following Table 2. Because the high fat and fructosediet is consisted of 73.3% corn starch and 26.7% butter powder, thecalorie obtained by the rats in 9 groups can be easily estimated.Moreover, the rats' weight data are recorded in following Table 3 afterexecuting the animal experiment for 10 days.

TABLE 2 Intake diet Intake water Daily intake calorie Group (g/day/rat)(mL/day/rat) (kcal/day/rat) NOR 23.95 ± 0.74^(c) 48.05 ± 3.45^(c)  80.00± 2.48^(a) HFFD 15.76 ± 1.29^(b) 31.58 ± 1.17^(ab) 104.82 ± 7.69^(c) MF14.78 ± 1.72^(ab) 32.44 ± 3.72^(ab)  98.38 ± 6.94^(ab) RMD 14.21 ±1.44^(a) 32.63 ± 3.46^(ab)  98.16 ± 7.10^(b) MS1X 14.46 ± 1.18^(ab)33.79 ± 1.79^(b)  98.53 ± 5.03^(bc) MS5X 14.37 ± 1.76^(ab) 33.57 ±3.47^(b)  97.91 ± 8.17^(bc) AK1X 14.85 ± 0.84^(ab) 32.21 ± 2.57^(ab) 99.85 ± 4.25^(bc) AK5X 14.08 ± 1.75^(a) 32.21 ± 2.63^(ab) 102.17 ±7.44^(bc) MS-AK 14.48 ± 0.90^(ab) 29.79 ± 1.27^(a)  96.26 ± 5.02^(b)

TABLE 3 Daily intake calorie Weight Group (kcal/day/rat) (g) NOR  80.00± 2.48^(a) 232.00 ± 21.33^(a) HFFD 104.82 ± 7.69^(c) 296.25 ± 45.3^(b)MF  98.38 ± 6.94^(ab) 268.75 ± 36.22^(ab) RMD  98.16 ± 7.10^(b) 292.75 ±44.84^(b) MS1X  98.53 ± 5.03^(bc) 285.75 ± 34.34^(b) MS5X  97.91 ±8.17^(bc) 275.13 ± 49.48^(b) AK1X  99.85 ± 4.25^(bc) 278.38 ± 22.03^(b)AK5X 102.17 ± 7.44^(bc) 262.25 ± 42.85^(ab) MS-AK  96.26 ± 5.02^(b)274.59 ± 19.89^(b)

From the data shown in Table 2 and Table 3, it can find that, the dailyintake calorie of the rats of all experimental groups are obviouslyhigher than the daily intake calorie of the rats in the NOR group.Moreover, comparing to the rats of HFFD group, the daily intake calorieof the rats in RMD, MS5X, and MS-AK group are lower. In addition, it canalso find that, the weight of the rats of all experimental groups areobviously heavier than the weight of the rats in the NOR group.Moreover, comparing to the rats of HFFD group, the weight of the rats inMF, RMD, MS1X, MS5X, AK1X, AK5X, and MS-AK group are lighter.

Determining Blood Sugar Regulating Effects Provided by the DifferentTest Samples on the SD Rats:

Before evaluating the blood sugar regulating ability of the differenttest samples, 12-hour fast must be executed on the rats of the 9experimental groups. After that, blood for determining the concentrationof fasting blood glucose (GLU-AC) is collected from the rats's rrbitalby using capillary tubes. On the other hand, to carry out oral glucosetolerance test (OGTT), the rats in the 9 experimental groups are orallyadministered with a glucose solution when starting the 12-hour fast; andthen, the rats has their blood tested again 30 minutes, 60 minutes and90 minutes after drinking the glucose solution.

Please refer to FIG. 1, where a curve plot of time versus blood glucose.Moreover, please refer to FIG. 2, which provides a statistical bar graphof group versus AUC (area under curve) of blood glucose. From FIG. 1, itcan easily find that, the glucose levels of the rats in HFFD group arelargely higher than the glucose levels of the rats in NOR group at 0 and30 minutes. On the other hand, from FIG. 2, it is able to know that therats in HFFD group have been suffered from Hyperglycemia because the AUC(area under curve) value of HFFD group is higher than the AUC value ofNOR group. However, all the AUC values of MF, MS1X, MS5X, AK5X, andMS-AK group are obviously lower than the HFFD group's AUC value.Moreover, the experimental data of FIG. 2 also prove that the5-fold-dose Ankaflavin shows better AUC reducing ability. Herein, it isworth noting that, although the combination of 1-fold-dose Ankaflavinand 1-fold-dose Monascin as well as 1-fold-dose Ankaflavin cannotlargely lower the AUC value, the AUC values of RMD group and AK1X groupare still lower than the HFFD group's AUC value.

Therefore, it is able to assume the cause resulted in the occurrence ofHyperglycemia in the rats of HFFD group is that the glucose cannot beeffectively utilized due to the failure of insulin receptors, whereinthe failure of insulin receptors is caused by a large amount ofadipocytes accumulation. However, according to the experimental dataprovided by FIG. 1 and FIG. 2, the blood glucose concentrations of therats fed with Monascin and/or Ankaflavin are effectively regulated. Suchresult implies that the insulin receptors in the rats fed with Monascinand/or Ankaflavin work normally for receiving insulin.

Determining Effects Provided by the Different Test Samples on GLU-AC,Insulin, Insulin Resistance, and Fructosamine Concentration of the Rats:

In normal situation, beta cells of pancreas would start to produceinsulin after the rats eat high energy diets. However, insulinresistance (IR) may be induced in the rats of HFFD group because thebeta cells are killed by ROS (Reactive oxygen species) induced byHyperglycermia. Based on above reasons, it needs to observe the effectsprovided by the different test samples on the GLU-AC, insulin, insulinresistance, and Fructosamine of the rats.

The blood collected by capillary tubes are disposed into a 2-mLmicrocentrifuge tube. After staying for 5 minutes, the microcentrifugetube carrying with blood is treated with a centrifugation process, andthen the serum of the blood is stored in an environment with −80 ° C. Inthis animal experiment, insulin determination is carried out by droppingthe serum onto an enzyme-linked immunosorbent assay (ELISA) insulin kit.Thereafter, the insulin resistance is then calculated by using followingequation: HOMA-IR 32 [insulin (μU/mL)*glucose(mmol/L)]/22.5. On theother hand, insulin determination is completed by dropping the serumonto a fructosamine assay kit. Therefore, the determination data ofblood glucose, insulin, insulin resistance, and fructosamine arerecorded and integrated in following Table 4 and Table 5.

TABLE 4 Blood glucose Insulin Group (mg/dL) (μU/mL) NOR  95.91 ±8.52^(ab) 40.04 ± 0.35^(a) HFFD 121.11 ± 4.96^(c) 55.60 ± 5.06^(c) MF102.38 ± 12.03^(ab) 41.55 ± 1.09^(a) RMD 105.63 ± 11.51^(b) 43.93 ±5.43^(ab) MS1X 100.25 ± 4.59^(ab) 43.12 ± 3.95^(ab) MS5X  95.50 ±6.00^(a) 40.45 ± 0.60^(a) AK1X  98.38 ± 11.01^(ab) 46.52 ± 5.24^(b) AK5X 97.38 ± 9.20^(ab) 45.73 ± 3.49^(b) MS-AK  99.51 ± 5.81^(ab) 41.35 ±1.52^(a)

TABLE 5 Insulin Fructosamine Group resistance (mM) NOR 10.10 ± 0.7^(a)0.71 ± 0.05^(a) HFFD 15.71 ± 1.85^(c) 1.32 ± 0.12^(d) MF 10.69 ±1.08^(ab) 0.88 ± 0.06^(c) RMD 12.01 ± 1.47^(b) 0.91 ± 0.09^(c) MS1X10.96 ± 1.3^(ab) 0.87 ± 0.07^(c) MS5X  9.77 ± 0.7^(a) 0.84 ± 0.06^(bc)AK1X 11.99 ± 2.08^(b) 0.90 ± 0.06^(c) AK5X 11.89 ± 1.78^(b) 0.88 ±0.06^(c) MS-AK 10.70 ± 1.24^(ab) 0.80 ± 0.06^(ab)

From Table 4, it can easily find that, the GLU-AC concentration of therats in HFFD group is greater than the GLU-AC concentration of the ratsin NOR group. However, comparing to the rats of HFFD group, the GLU-ACconcentrations of the rats in MF, RMD, MS1X, MS5X, AK1X, AK5X, and MS-AKgroup are largely lowered. Moreover, it is worth noting that, the GLU-AClevel of the rats in MS5X group is almost equal to the GLU-AC level ofthe rats in NOR group. Such result implies that the 5-fold-dose Monascinpossesses high-efficiency blood sugar regulating ability.

From Table 4, it can also find that, the insulin concentration of therats in HFFD group is greater than the insulin concentration of the ratsin NOR group. However, comparing to the rats of HFFD group, the insulinconcentrations of the rats in MF, RMD, MS1x, MS5X, AK1X, AK5X, and MS-AKgroup are largely lowered. Moreover, it is worth noting that, theinsulin level of the rats in MS5X group is almost equal to the insulinlevel of the rats in NOR group. Such result implies that the 5-fold-doseMonascin possesses high-efficiency insulin regulating ability.

Moreover, from Table 5, it can easily find that, the insulin resistancevalue of the rats in HFFD group is greater than the insulin resistancevalue of the rats in NOR group. However, comparing to the rats of HFFDgroup, the insulin resistance value of the rats in MF, RMD, MS1X, MS5X,AK1X, AK5X, and MS-AK group are largely lowered. Moreover, it is worthnoting that, the insulin resistance value of the rats in MS5X group isalmost equal to the insulin resistance value of the rats in NOR group.Such result implies that the 5-fold-dose Monascin possesseshigh-efficiency insulin resistance value lowering ability.

From Table 5, it can also find that, the fructosamine concentration ofthe rats in HFFD group is greater than the fructosamine concentration ofthe rats in NOR group. However, comparing to the rats of HFFD group, thefructosamine concentration of the rats in MF, RMD, MS1X, MS5X, AK1X,AK5X, and MS-AK group are largely lowered. So that, the experimentaldata provided by Table 4 and Table 5 prove that the Monascin andAnkaflavin indeed possess functionality to regulate blood glucose,insulin, insulin resistance, and fructosamine.

Determining effects provided by the different test samples on liver,kidney, and adipose tissue weight of the rats:

Insulin is used for impelling the absorption and utilization of bloodglucose in liver, muscle and adipose tissue. Because white adiposetissue (WAT) is used for storing triglycerides (TG) transformed fromblood glucose, a large amount of accumulation of adipocytes would causethe occurrence of inflammatory response so as to induce lipolysisaction. Therefore, the inflammatory-induced lipolysis action wouldproduce a large amount of glycerin and free fatty acid (FFA), so as toaggravate the production of Hyperglycemia, fatty liver, and high bloodketone. Based on above reasons, the effects provided by the differenttest samples on liver, kidney, and adipose tissue weight of the rats areneeded to be determined.

For carrying out the determination of liver, kidney, and adipose tissueweight, it needs to sacrifice the rats. After sacrificing the rat, bloodto be determined is collected from the intraperitoneal of the rat byusing syringes, and then the collected blood are disposed into a 2-mLmicrocentrifuge tube. After staying for 5 minutes, the microcentrifugetube carrying with blood is treated with a centrifugation process, andthen the serum of the blood is stored in an environment with −20 ° C.After that, the liver, kidney, and adipose tissue are taken out of therat.

Following Table 6 has recorded with weight data of the liver and kidneytissue. From Table 6, it can easily find that, the liver weights of therats in HFFD group are largely higher than the liver weights of the ratsin NOR group. However, comparing to the rats of HFFD group, the liverweights of the rats in MF, RMD, MS1X, MS5X, AK1X, AK5X, and MS-AK groupare largely lowered. Herein, it is worth noting that, the liver weightdata of the rats in MS5X group is almost equal to the liver weight dataof the rats in NOR group. Such result implies that the 5-fold-doseMonascin possesses high-efficiency liver weight regulating ability.

TABLE 6 Group Liver weight Kidney weight NOR 13.67 ± 1.07^(a) 3.78 ±0.16^(a) HFFD 22.08 ± 2.09^(d) 3.42 ± 0.26^(b) MF 15.61 ± 1.53^(bc) 3.64± 0.26^(ab) RMD 16.47 ± 1.85^(c) 3.62 ± 0.20^(ab) MS1X 15.25 ±1.64^(abc) 3.61 ± 0.20^(ab) MS5X 14.62 ± 1.84^(ab) 3.71 ± 0.40^(ab) AK1X15.36 ± 1.09^(bc) 3.72 ± 0.31^(ab) AK5X 15.58 ± 1.32^(bc) 3.55 ±0.29^(ab) MS-AK 15.70 ± 1.00^(bc) 3.58 ± 0.25^(ab)

Following Table 7 has recorded with weight data of the peri-adrenal andepididymal adipose tissue. From Table 7, it can easily find that, theweights of peri-adrenal and epididymal adipose tissue of the rats inHFFD group are largely higher than the weights of peri-adrenal andepididymal adipose tissue of the rats in NOR group. However, comparingto the rats of HFFD group, the weights of peri-adrenal and epididymaladipose tissue of the rats in MF, RMD, MS1X, MS5X, AK1X, AK5X, and MS-AKgroup are largely lowered.

TABLE 7 Percentage of Percentage of Occupying percentage of weight ofweight of summation of the peri-adrenal epididymal weights ofperi-adrenal adipose adipose and epididymal adipose tissue tissue tissuein body Fat Group (%) (%) (%) NOR 1.39 ± 0.24^(a) 1.11 ± 0.15^(a) 2.54 ±0.38^(a) HFFD 3.61 ± 0.47^(c) 2.26 ± 0.46^(c) 5.88 ± 0.82^(c) MF 3.33 ±0.66^(bc) 1.83 ± 0.43^(b) 4.27 ± 1.43^(bc) RMD 3.04 ± 0.65^(b) 1.95 ±0.39^(bc) 4.98 ± 0.50^(c) MS1X 2.99 ± 0.60^(b) 1.97 ± 0.33^(bc) 5.12 ±0.84^(bc) MS5X 3.15 ± 0.45^(bc) 1.79 ± 0.33^(b) 4.97 ± 0.80^(bc) AK1X2.75 ± 0.37^(b) 1.96 ± 0.4^(bc) 4.32 ± 0.59^(b) AK5X 2.96 ± 0.43^(b)1.69 ± 0.3^(b) 4.30 ± 0.53^(b) MS-AK 2.99 ± 0.60^(b) 2.02 ± 0.39^(bc)5.06 ± 0.43^(bc)

The high fat and fructose diet may also cause the rats suffer fromHypertriglyceridemia, so as to damage the liver. Following Table 8 hasrecorded with data of triglycerides (TG) and total cholesterol (TC).From Table 8, it can easily find that, the concentrations oftriglycerides and total cholesterol of the rats in HFFD group arelargely higher than the concentrations of triglycerides and totalcholesterol of the rats in NOR group. However, comparing to the rats ofHFFD group, the concentrations of triglycerides and total cholesterol ofthe rats in MF, RMD, MS1X, MS5X, AK1X, AK5X, and MS-AK group are largelylowered.

TABLE 8 TG TC Group (mg/dL) (mg/dL) NOR  82.25 ± 7.85^(a) 75.00 ±7.5^(b) HFFD 255.00 ± 37.01^(e) 84.50 ± 11.88^(c) MF 170.88 ± 46.04^(d)68.50 ± 9.93^(ab) RMD 139.13 ± 39.3^(cd) 73.00 ± 10.10^(ab) MS1X 136.63± 29.66^(cd) 70.00 ± 2.88^(ab) MS5X  99.88 ± 18.90^(ab) 66.75 ±7.11^(ab) AK1X 138.75 ± 47.07^(cd) 66.50 ± 7.87^(ab) AK5X 137.63 ±33.21^(cd) 64.25 ± 8.94^(a) MS-AK 129.88 ± 18.15^(bc) 64.63 ± 6.39^(a)

So that, the experimental data provided by Table 6, Table 7 and Table 8prove that the Monascin and Ankaflavin indeed possess functionality tolower insulin resistance by regulating insulin, so as to reduce theliver, kidney and adipose tissue weight. Moreover, the Monascin andAnkaflavin also possess functionality to lower the TG level in adiposetissue by regulating blood glucose concentration.

On the other hand, in normal situation, human serum would includeadiponectin of 5-30 μg/mL for maintaining the balance between glucoseand lipids. Adiponectin dose not only play an important role in theformation of insulin resistance, but also has close relationship withTG.

Please refer to FIG. 3, which provides a statistical bar graph ofadiponectin expression in adipose tissue. From Table FIG. 3, it caneasily find that, the percentage of adiponectin expression of the ratsin HFFD group is lower than the percentage of adiponectin expression ofthe rats in NOR group. However, comparing to the rats of HFFD group, thepercentage of adiponectin expression of the rats in MF, RMD, MS1X, MS5X,AK1X, AK5X, and MS-AK group is largely enhanced. So that, theexperimental data provided by FIG. 3 prove that the Monascin andAnkaflavin indeed possess functionality to regulate the adiponectinlevel in adipose tissue.

Determining Effects Provided by the Different Test Samples on ROSProduced in Liver:

One of key factors to induce the occurrence of diabetes mellitus andmetabolism syndrome is Reactive Oxygen Species (ROS) resulted from Hyperglycemia. Please refer to FIG. 4, which provides a statistical bargraph of ROS concentration in liver. From Table FIG. 4, it can easilyfind that, the ROS level of the rats in HFFD group is largely higherthan the ROS level of the rats in NOR group. However, comparing to therats of HFFD group, the ROS levels of the rats in MF, RMD, MS1X, MS5X,AK1X, AK5X, and MS-AK group are largely lowered. So that, theexperimental data provided by FIG. 4 prove that the Monascin andAnkaflavin indeed possess functionality to reduce the ROS concentrationin liver.

Determining Effects Provided by the Different Test Samples onInflammation Factors in Adipose Tissue:

The adipose tissue of an obesity patient may releases inflammationfactors such as hypoxia-inducible factor 1α (HIF-1α), tumor necrosisfactor-α (TNF-α) and interleukin (IL), wherein the excessive amount ofinflammation factors would induce lipolysis action to produce a largeamount of glycerin and free fatty acid (FFA), so as to aggravate theproduction of Hyperglycemia, fatty liver, and high blood ketone. Pleaserefer to FIG. 5, which provides a statistical bar graph of TNF-αexpression in adipose tissue. From Table FIG. 5, it can easily findthat, the percentage of TNF-α expression of the rats in HFFD group islargely higher than the percentage of TNF-α expression of the rats inNOR group. However, comparing to the rats of HFFD group, the percentagesof TNF-α expression of the rats in MF, RMD, MS1X, MS5X, AK1X, AK5X, andMS-AK group are largely reduced.

Continuously, please refer to FIG. 6 and FIG. 7, where a statistical bargraph of GLUT-2 expression in adipose tissue and a statistical bar graphof GLUT-4 expression in adipose tissue are shown. From Table FIG. 6, itcan easily find that, the percentage of GLUT-2 expression of the rats inHFFD group is largely lower than the percentage of GLUT-2 expression ofthe rats in NOR group. However, comparing to the rats of HFFD group, thepercentages of GLUT-2 expression of the rats in MF, RMD, MS1X, MS5X,AK1X, AK5X, and MS-AK group are largely enhanced. Furthermore, fromTable FIG. 7, it can also find that, the percentage of GLUT-4 expressionof the rats in HFFD group is largely lower than the percentage of GLUT-4expression of the rats in NOR group. However, comparing to the rats ofHFFD group, the percentages of GLUT-4 expression of the rats in MF, RMD,MS1X, MS5X, AK1X, AK5X, and MS-AK group are largely enhanced. So that,the experimental data provided by FIG. 5, FIG. 6 and FIG. 7 prove thatthe Monascin and Ankaflavin indeed possess functionality to enhance theGLUT (glucose transporter) expression in adipose tissue by inhibitingthe expression of TNF-α.

Please refer to FIG. 8 and FIG. 9, where a statistical bar graph of IL-6expression in adipose tissue and a statistical bar graph of IL-1βexpression in adipose tissue are provided. From Table FIG. 8, it caneasily find that, the percentage of IL-6 expression of the rats in HFFDgroup is largely higher than the percentage of IL-6 expression of therats in NOR group. However, comparing to the rats of HFFD group, thepercentages of IL-6 expression of the rats in MF, RMD, MS1X, MS5X, AK1X,AK5X, and MS-AK group are largely lowered. Furthermore, from Table FIG.9, it can also find that, the percentage of IL-1β expression of the ratsin HFFD group is largely higher than the percentage of IL-1β expressionof the rats in NOR group. However, comparing to the rats of HFFD group,the percentages of IL-1β expression of the rats in MF, RMD, MS1X, MS5X,AK1X, AK5X, and MS-AK group are largely lowered.

Continuously, please refer to FIG. 10, which illustrates a statisticalbar graph of HIF-1α expression in adipose tissue. From Table FIG. 10, itcan easily find that, the percentage of HIF-1α expression of the rats inHFFD group is largely higher than the percentage of HIF-α expression ofthe rats in NOR group. However, comparing to the rats of HFFD group, thepercentages of HIF-1α expression of the rats in MF, RMD, MS1X, MS5X,AK1X, AK5X, and MS-AK group are largely lowered. So that, theexperimental data provided by FIG. 8, FIG. 9 and FIG. 10 prove that theMonascin and Ankaflavin indeed possess functionality to reduce the ROSconcentration produced in liver.

Determining Effects Provided by the Different Test Samples on LiverTissue:

Liver is rich in various enzyme, such as aspartate aminotransferase(AST) and alanine aminotransferase (ALT). When liver is subjected todamage, AST and ALT would be released into blood. Please refer to FIG.11, where histomorphology images of liver slices are provided. From FIG.11, it can find that, the liver tissue taken out from the rats of HFFDgroup has become fatty liver (indicated by arrow in FIG. 11) due toexcessive amount of fat accumulation. However, comparing to the rats ofHFFD group, the formation of fatty liver of the rats in MF, RMD, MS1X,MS5X, AK1X, AK5X, and MS-AK group has been alleviated or solved.

Following Table 8 has recorded with AST and ALT data. From Table 8, itcan easily find that, the AST and ALT levels of the rats in HFFD groupare almost equal to the AST and ALT levels of the rats in NOR group.Such result implies that the liver of the hyperglycemia-induced DM ratdoes not be damaged. However, comparing to the rats of HFFD group, theAST and ALT levels of the rats in MF, RMD, MS1X, MS5X, AK1X, AK5X, andMS-AK group are largely lowered.

TABLE 8 AST ALT Group (U/L) (U/L) NOR 71.00 ± 8.45^(b) 34.13 ± 2.59^(e)HFFD 75.00 ± 11.75^(b) 31.88 ± 2.80^(e) MF 71.63 ± 6.59^(b) 25.13 ±3.83^(cd) RMD 58.50 ± 8.98^(a) 24.25 ± 5.55^(d) MS1X 61.50 ± 7.05^(a)25.38 ± 2.33^(bcd) MS5X 63.63 ± 5.93^(a) 25.50 ± 3.16^(abc) AK1X 59.63 ±4.96^(a) 24.75 ± 3.01^(ab) AK5X 64.75 ± 11.85^(a) 18.88 ± 3.44^(a) MS-AK80.25 ± 16.22^(b) 31.38 ± 3.81^(e)

On the other hand, Hyperglycemia would also damage glomeruli of kidney,such that the metabolic wastes cannot be fully filtered out of the bloodthrough the kidney, especially to the creatinine and urea. FollowingTable 9 has recorded with creatinine data. From Table 9, it can easilyfind that, the creatinine concentration of the rats in HFFD group isalmost equal to the creatinine concentration of the rats in NOR group.However, comparing to the rats of HFFD group, the creatinineconcentration of the rats in MF, RMD, MS1X, MS5X, AK1X, AK5X, and MS-AKgroup is largely lowered.

TABLE 9 Creatinine Group (mg/dL) NOR 0.45 ± 0.05^(ab) HFFD 0.53 ±0.07^(b) MF 0.46 ± 0.05^(ab) RMD 0.39 ± 0.10^(ab) MS1X 0.50 ± 0.09^(ab)MS5X 0.46 ± 0.05^(ab) AK1X 0.38 ± 0.05^(ab) AK5X 0.43 ± 0.09^(a) MS-AK0.48 ± 0.07^(ab)

Therefore, through above descriptions, the composition for regulatingblood sugar provided by the present invention has been introducedcompletely and clearly; in summary, the present invention includes theadvantages of:

(1) This blood sugar regulating composition merely comprises at leastone yellow pigment extracted from a red mold product, wherein the saidyellow pigment is Monascin, Ankaflavin, or combination of Monascin andAnkaflavin. Moreover, results of a variety of animal experiments haveproved that this blood sugar regulating composition indeed possess thefunctionalities of: lowering Hyperglycemia induced by high energy diet,alleviating ROS and inflammatory caused by the Hyperglycemia, reduce ASTand ALT value of liver as well as sarcosine value of kidney.

The above description is made on embodiments of the present invention.However, the embodiments are not intended to limit scope of the presentinvention, and all equivalent implementations or alterations within thespirit of the present invention still fall within the scope of thepresent invention.

What is claimed is:
 1. A composition for regulating blood sugar,comprising a yellow pigment extracted from a red mold product, whereinthe said yellow pigment is Monascin, and a daily dosage of the Monascinfor an adult user to regulate blood sugar is above 3 mg.
 2. Thecomposition for regulating blood sugar of claim 1, wherein the red moldproduct is produced by inoculating a Monascus purpureus to a substrateand then subjecting the inoculated substrate with a culturing and dryingprocess.
 3. The composition for regulating blood sugar of claim 1,wherein the Monascin with the daily dosage can also lower insulinresistance induced by Hyperglycemia.
 4. The composition for regulatingblood sugar of claim 1, wherein the Monascin with the daily dosage canalso lower the increasing of Triglycerides (TG) induced byHyperglycemia.
 5. The composition for regulating blood sugar of claim 1,wherein the Monascin with the daily dosage can also lower the increasingof ROS (Reactive oxygen species) induced by Hyperglycemia.
 6. Thecomposition for regulating blood sugar of claim 1, wherein the Monascinwith the daily dosage can also alleviate the decreasing of glucosetransporter (GLUT) caused by Hyperglycemia.
 7. The composition forregulating blood sugar of claim 1, wherein the Monascin with the dailydosage can also lower the increasing of aspartate aminotransferase (AST)and alanine aminotransferase (ALT) in liver induced by Hyperglycemia. 8.The composition for regulating blood sugar of claim 1, wherein theMonascin with the daily dosage can also lower the increasing ofsarcosine in kidney induced by Hyperglycemia.
 9. The composition forregulating blood sugar of claim 2, wherein the substrate is a ricesubstrate or a Dioscorea substrate.
 10. A composition for regulatingblood sugar, comprising a yellow pigment extracted from a red moldproduct, wherein the said yellow pigment is Ankaflavin, and a dailydosage of the Ankaflavin for an adult user to regulate blood sugar isabove 1.5 mg.
 11. The composition for regulating blood sugar of claim10, wherein the red mold product is produced by inoculating a Monascuspurpureus to a substrate and then subjecting the inoculated substratewith a culturing and drying process.
 12. The composition for regulatingblood sugar of claim 10, wherein the Ankaflavin with the daily dosagecan also lower insulin resistance induced by Hyperglycemia.
 13. Thecomposition for regulating blood sugar of claim 10, wherein theAnkaflavin with the daily dosage can also lower the increasing ofTriglycerides (TG) induced by Hyperglycemia.
 14. The composition forregulating blood sugar of claim 10, wherein the Ankaflavin with thedaily dosage can also lower the increasing of ROS (Reactive oxygenspecies) induced by Hyperglycemia.
 15. The composition for regulatingblood sugar of claim 10, wherein the Ankaflavin with the daily dosagecan also alleviate the decreasing of glucose transporter (GLUT) causedby Hyperglycemia.
 16. The composition for regulating blood sugar ofclaim 10, wherein the Ankaflavin with the daily dosage can also lowerthe increasing of aspartate aminotransferase (AST) and alanineaminotransferase (ALT) in liver induced by Hyperglycemia.
 17. Thecomposition for regulating blood sugar of claim 10, wherein theAnkaflavin with the daily dosage can also lower the increasing ofsarcosine in kidney induced by Hyperglycemia.
 18. The composition forregulating blood sugar of claim 11, wherein the substrate is a ricesubstrate or a Dioscorea substrate.
 19. A composition for regulatingblood sugar, comprising two yellow pigments extracted from a red moldproduct, wherein the said two yellow pigment are Monascin with firstdaily dosage of above 3 mg and Ankaflavin with second daily dosage ofabove 1.5 mg, therefore a total daily dosage of the composition for anadult user to regulate blood sugar is above 4.5 mg.
 20. The compositionfor regulating blood sugar of claim 19, wherein the red mold product isproduced by inoculating a Monascus purpureus to a substrate and thensubjecting the inoculated substrate with a culturing and drying process.21. The composition for regulating blood sugar of claim 19, wherein thecomposition with the total daily dosage can also lower insulinresistance induced by Hyperglycemia.
 22. The composition for regulatingblood sugar of claim 19, wherein the composition with the total dailydosage can also lower the increasing of Triglycerides (TG) induced byHyperglycemia.
 23. The composition for regulating blood sugar of claim19, wherein the composition with the total daily dosage can also lowerthe increasing of ROS (Reactive oxygen species) induced byHyperglycemia.
 24. The composition for regulating blood sugar of claim19, wherein the composition with the total daily dosage can alsoalleviate the decreasing of glucose transporter (GLUT) caused byHyperglycemia.
 25. The composition for regulating blood sugar of claim19, wherein the composition with the total daily dosage can also lowerthe increasing of aspartate aminotransferase (AST) and alanineaminotransferase (ALT) in liver induced by Hyperglycemia.
 26. Thecomposition for regulating blood sugar of claim 19, wherein thecomposition with the total daily dosage can also lower the increasing ofsarcosine in kidney induced by Hyperglycemia.
 27. The composition forregulating blood sugar of claim 20, wherein the substrate is a ricesubstrate or a Dioscorea substrate.
 28. A composition for regulatingblood sugar, being a red mold product produced by inoculating a Monascuspurpureus to a substrate and then subjecting the inoculated substratewith a culturing and drying process; wherein a daily dosage of the redmold product for an adult user to regulate blood sugar is above 1 g. 29.The composition for regulating blood sugar of claim 28, wherein thesubstrate is a rice substrate or a Dioscorea substrate.
 30. Thecomposition for regulating blood sugar of claim 28, wherein the red moldproduct with the daily dosage can also lower insulin resistance inducedby Hyperglycemia.
 31. The composition for regulating blood sugar ofclaim 28, wherein the composition with the total daily dosage can alsolower the increasing of Triglycerides (TG) induced by Hyperglycemia. 32.The composition for regulating blood sugar of claim 28, wherein thecomposition with the total daily dosage can also lower the increasing ofROS (Reactive oxygen species) induced by Hyperglycemia.
 33. Thecomposition for regulating blood sugar of claim 28, wherein thecomposition with the total daily dosage can also alleviate thedecreasing of glucose transporter (GLUT) caused by Hyperglycemia. 34.The composition for regulating blood sugar of claim 28, wherein thecomposition with the total daily dosage can also lower the increasing ofaspartate aminotransferase (AST) and alanine aminotransferase (ALT) inliver induced by Hyperglycemia.
 35. The composition for regulating bloodsugar of claim 28, wherein the composition with the total daily dosagecan also lower the increasing of sarcosine in kidney induced byHyperglycemia.